Arsenic Toxicity in Male Reproduction and Development

Abstract

Arsenic is a toxic metalloid that exists ubiquitously in the environment, and affects global health problems due to its carcinogenicity. In most populations, the main source of arsenic exposure is the drinking water. In drinking water, chronic exposure to arsenic is associated with increased risks of various cancers including those of skin, lung, bladder, and liver, as well as numerous other non-cancer diseases including gastrointestinal and cardiovascular diseases, diabetes, and neurologic and cognitive problems. Recent emerging evidences suggest that arsenic exposure affects the reproductive and developmental toxicity. Prenatal exposure to inorganic arsenic causes adverse pregnancy outcomes and children’s health problems. Some epidemiological studies have reported that arsenic exposure induces premature delivery, spontaneous abortion, and stillbirth. In animal studies, inorganic arsenic also causes fetal malformation, growth retardation, and fetal death. These toxic effects depend on dose, route and gestation periods of arsenic exposure. In males, inorganic arsenic causes reproductive dysfunctions including reductions of the testis weights, accessory sex organs weights, and epididymal sperm counts. In addition, inorganic arsenic exposure also induces alterations of spermatogenesis, reductions of testosterone and gonadotrophins, and disruptions of steroidogenesis. However, the reproductive and developmental problems following arsenic exposure are poorly understood, and the molecular mechanism of arsenic-induced reproductive toxicity remains unclear. Thus, we further investigated several possible mechanisms underlying arsenic-induced reproductive toxicity.

Arsenic trioxide exposure impairs testicular morphology in adult male mice and consequent fetus viability

“…First, As 2 O 3 metabolites accumulate mainly in liver, kidneys, and blood and elevated ROS production generates systemic toxicity, affecting the testis (Thomas, Styblo, and Lin 2001). Secondly, chemicals also may affect the hypothalamic-pituitary and change LH and FSH plasma concentrations, resulting in an impairment of Leydig cell function and decreased testosterone production; and finally, the toxic chemical might exert an inhibitory action directly on testis (Kim and Kim 2015). These substances might reach the immune-privileged environment provided by the blood-testis barrier (BTB) and resultant oxidative stress might damage the Sertoli supporting cells by disrupting the inter-Sertoli tight junctions.…”

State of the science review of the health effects of inorganic arsenic: Perspectives for future research

“…i As causes deleterious effects on human reproduction. Both teratogenic and developmental toxicities have been characterized . However, because of the potential confounding factors and recall bias associated with both ecological and retrospective study designs, it has been pointed out that stronger study designs would increase the statistical power and produce stronger results.…”

Environmental exposure of arsenic and fluoride and their combined toxicity: A recent update

“…It also inhibits pyruvate dehydrogenase activity by binding to the lipoic acid moiety (Flora, Bhadauria, Kannan, & Singh, ). Methylated arsenical (MMA) is an inhibitor of GSH reductase and thioredoxin reductase (Kim & Kim, ). As blocks the Krebs cycle and interrupts oxidative phosphorylation.…”